By Clara Tung 董卓衡
“In the human body, there are about 37.2 trillion cells working 24/7 and energetically.” This informative and inspiring prologue of the animation, Cells at Work!, suggested that every part of our bodies has to “work” coordinately, and some constantly. The vivid visualization of the cells categorized by the adorable characters has given us a clearer understanding of the interaction and major functions of body cells.
Meet the Characters
Red Blood Cell (RBC)
In the Animation
- Energetic and responsible in her job
- Easily lose her direction
- Need to go through the narrowest road and deliver oxygen to the corresponding “residents” which represent body cells of various organs (Indeed, in reality, capillaries are super narrow that only one RBC can pass through each time!)
- Account for 45% of the blood components by volume 
- Color: Bright red when carrying oxygen; dark red when not carrying oxygen
- Shape: Biconcave disc with no nucleus when mature
- Each RBC contains 300 million hemoglobin molecules . Each hemoglobin contains four hemes and the central iron atom in each heme can bind one oxygen molecule. Therefore, each hemoglobin can carry four oxygen molecules.
- Transport oxygen from lungs to cells
White Blood Cell (WBC) – Neutrophil
In the Animation
- Usually calm but won’t spare the enemies once he notices them
- When he senses the enemies, the sign with an O-shaped pattern on his hat (receptor) will pop up.
- Neutrophil, the WBC depicted in the animation, represents the most abundant type (~70%) of WBC in the blood .
- Survive only for a few hours to several days in circulation [4, 5]
- Usually the first cells to migrate to the site of infection
- There are other types of WBC: eosinophil, basophil, lymphocyte and monocyte
- Kill invading microbes by 1) phagocytosis (engulfing and digesting), 2) degranulation (releasing antimicrobial substances) and 3) “neutrophil extracellular traps” (NETs; throwing a DNA net with antimicrobial substances to trap and kill the microbes while sacrificing itself) 
Killer T Cell (Cytotoxic T Cell)
In the Animation
- Obnoxious and irritable
- Look like a muscular soldier and involve in hand-to-hand combat to exert control
- Differentiate in bone marrow and mature in thymus
- Bind to cancerous or infected cells and kill them. One way is to release proteins that poke holes on the plasma membrane of the target cell.
In the Animation
- Depicted like an elegant young lady, but contrary to her appearance, she has a great ability to beat and kill invaders with her large weapons, such as mallet and axe.
- Be the teacher of erythroblasts (immature RBCs) in the “red bone marrow school”
- Differentiate from monocyte; mature into macrophage after monocyte leaves blood vessel and migrates into tissue
- Kill pathogens by phagocytosis
- Help recruit other immune cells in an immune response.
- Support the development of erythroblasts
In the Animation
- Petite and adorable; depicted like a little girl
- Tools and equipment: a yellow “no entry” flag, a whistle and different repair materials
- The smallest “blood cell” with a diameter of only 2-3 μm (only 20% of the diameter of RBC – that’s why they are depicted as children)
- Not a true cell, but cell debris without nucleus
- Produced from the fragmentation of megakaryocytes (a large nucleated bone marrow cell) 
- Can be stimulated by the breakage in blood vessel wall
- Participate in the formation of blood clot to stop further bleeding and invasion of pathogens
Case Study: The Red Bone Marrow School – Macrophage and Erythroblast
The functions of macrophage are not merely about the immune defense in our body; macrophage also plays a critical role in erythropoiesis, in other words, RBC development. In episode 6, the process is depicted as the “schooling of RBC”. Let’s focus on the following two important concepts mentioned!
The First Concept: Macrophage as a Teacher of RBC
- What is the “school of RBCs” in reality?
The “school” in the animation represents the red bone marrow, where RBCs are produced. In the red bone marrow, there are structures called “erythroblastic islands” where many erythroblasts surround a central macrophage. The central macrophage is similar to the teacher at school and it nurtures the nearby erythroblasts. 
- What exactly does macrophage “teach” erythroblasts?
It is suggested that macrophages actively assist in the development of erythroblasts by providing iron (recycled from the aged or damaged RBCs) for heme synthesis [7, 8]. They also provide proliferative and survival signals to the erythroblasts, and are involved in erythroblast enucleation .
The Second Concept: Erythroblast Enucleation
- How does macrophage help with the erythroblast enucleation (removal of nucleus)?
In the final stage of RBC maturation, erythroblast has to expel its nucleus, and macrophage helps phagocytose the expelled nucleus . In the animation, this is depicted as the graduation ceremony in which the fur balls on the students’ berets are removed by the teacher (macrophage).
- What is the importance of the removal of nucleus?
After enucleation, RBC will have extra capacity for more hemoglobin, and hence, more oxygen. It also allows RBC to turn into its distinctive biconcave shape which facilitates the diffusion of oxygen by increasing the surface area to volume ratio and shortening the diffusion distance from outside to the center of the cell. Also, it allows RBC to squeeze itself in order to travel through the narrow blood capillaries all over the body.
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 Smith DW. The molecular biology of mammalian hemoglobin synthesis. Ann Clin Lab Sci. 1980;10(2):116-22.
 Rosales C. Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?. Front Physiol. 2018;9:113. doi:10.3389/fphys.2018.00113
 Bratton DL, Henson PM. Neutrophil clearance: when the party is over, clean-up begins. Trends Immunol. 2011;32(8):350-57. doi:10.1016/j.it.2011.04.009
 Machlus KR, Thon JN, Italiano JE Jr. Interpreting the developmental dance of the megakaryocyte: a review of the cellular and molecular processes mediating platelet formation. Br J Haematol. 2014;165(2):227-36. doi: 10.1111/bjh.12758
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 Sukhbaatar N, Weichhart T. Iron Regulation: Macrophages in Control. Pharmaceuticals (Basel). 2018;11(4):137. doi:10.3390/ph11040137